The program of research proposed in this investigation will employ correlative immunocytochemistry (both light and electron microscopic) and radio-immunoassay to delineate the cortiicotropin releasing factor (CRF) neuronal systems of the central nervous system. CRF immunopositive neurons have been demonstrated to reside in the paraventricular nucleus (PVN) of the hypothalamus and a major fiber projection from these cells was traced to the perivascular contact zone of the median eminence (ME) and proximal neural stem. An analysis of the interrelationships of the CRF system with neurons that produce other peptide hormones (especially vasopressin and ACTH) both within the PVN and the ME is proposed. This program of research will confront such fundamental issues as: 1) What are the interrelationships of the CRF system in the hypothalamus? 2) Do extrahypothalamic CRF neuronal systems exist? If so, how do these neurons interconnect with known systems related to neurogenic stress? 3) Does the hypothalamic CRF system demonstrate a circadian rhythmicity similar to that of ACTH and corticosteroids? Is there a sexual dimorphism of the CRF system? 4) What are the effects of experimental manipulation (e.g. hypophysectomy, adrenalectomy, corticosterone or dexamethasone treatment. ether and restraint stress, ablation of the suprachiasmatic nucleus) on the hypothalamo-pituitary- adrenal systems? This program of research will provide answers to these very basic, but important definitions of the neuroendocrine component of this endocrine axis. Basic information gleaned from these studies will provide the foundation to the understanding of clinical endocrinopathies related to the brain-pituitary-adrenal axis.